Regulation of the Neurospora circadian clock by an RNA helicase

Ping Cheng, Qun He, Qiyang He, Lixin Wang, Yi Liu

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

The eukaryotic circadian oscillators consist of autoregulatory negative-feedback loops. FRQ, WC-1, and WC-2 are three known components of the negative-feedback loop of the Neurospora circadian oscillator. FRQ represses its own transcription by interacting with the WC-1/WC-2 complex and inhibiting WC's role in transcriptional activation. Here we show that all FRQ associates with FRH, an essential DEAD box-containing RNA helicase in Neurospora. The budding yeast homolog of FRH, Dob1p/Mtr4p, is a cofactor of exosome, an important regulator of RNA metabolism in eukaryotes. Down-regulation of FRH by inducible expression of a hairpin RNA leads to low levels of FRQ but high levels of frq RNA and the abolishment of circadian rhythmicities. FRH is associated with the WC complex and this interaction is maintained in a frq null strain. Disruption of the FRQ-FRH complex by deleting a domain in FRQ eliminates the FRQ-WC interaction, suggesting that FRH mediates the interaction between FRQ and the WC complex. These data demonstrate that FRH is an essential component in the circadian negative-feedback loop and reveal an unexpected role of an RNA helicase in regulating gene transcription.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalGenes and Development
Volume19
Issue number2
DOIs
StatePublished - Jan 15 2005

Keywords

  • Exosome
  • FRH
  • Frequency
  • Mtr4p
  • RNAi
  • White collar-1

ASJC Scopus subject areas

  • General Medicine

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